TY - JOUR
T1 - Additional molecular and clinical evidence open the way to definitive
IARC classification of the BRCA1 c.5332G > A (p.Asp1778Asn) variant
AU - Minucci, A
AU - Lalle, M
AU - De Leo, R
AU - Mazzuccato, G
AU - Scambia, G
AU - Urbani, Andrea
AU - Fagotti, Anna
AU - Concolino, P
AU - Capoluongo, E
PY - 2019
Y1 - 2019
N2 - Objectives: In silico splicing analysis, a mini-gene assay and splicing data, obtained using RNA from blood samples, have shown that the BRCA1 c.5332G > A variant induces exon 21 skipping. However, despite these evidences, up to date, this variant is unclassified.\r\nThe aim of this study is to provide further molecular and clinical evidence for the BRCA1 c.5332G > A variant in a patient with high grade serous ovarian carcinoma (HGSOC) to allow a definitive classification of this variant.\r\nDesign and method: The effect of the BRCA1 c.5332G > A variant on RNA splicing was evaluated by amplifying regions of BRCA1 from the cDNA of the patient. Loss of heterozygosity (LOH) in tumor tissue was also investigated.\r\nResults: The c.5332G > A allele causes significantly aberrant splicing of the BRCA1 exon 21. Evaluation of the c.5332A allele in tumor tissue highlights a possible loss of heterozygosity, supporting her pathogenic effect.\r\nConclusions: Our results regarding the c.5332G > A variant confirm that it contributed to predisposition and onset of ovarian carcinoma in the patient. We propose to classify this variant as 'likely-pathogenic' (class IV).
AB - Objectives: In silico splicing analysis, a mini-gene assay and splicing data, obtained using RNA from blood samples, have shown that the BRCA1 c.5332G > A variant induces exon 21 skipping. However, despite these evidences, up to date, this variant is unclassified.\r\nThe aim of this study is to provide further molecular and clinical evidence for the BRCA1 c.5332G > A variant in a patient with high grade serous ovarian carcinoma (HGSOC) to allow a definitive classification of this variant.\r\nDesign and method: The effect of the BRCA1 c.5332G > A variant on RNA splicing was evaluated by amplifying regions of BRCA1 from the cDNA of the patient. Loss of heterozygosity (LOH) in tumor tissue was also investigated.\r\nResults: The c.5332G > A allele causes significantly aberrant splicing of the BRCA1 exon 21. Evaluation of the c.5332A allele in tumor tissue highlights a possible loss of heterozygosity, supporting her pathogenic effect.\r\nConclusions: Our results regarding the c.5332G > A variant confirm that it contributed to predisposition and onset of ovarian carcinoma in the patient. We propose to classify this variant as 'likely-pathogenic' (class IV).
KW - Hereditary ovarian cancer
KW - Splicing variant
KW - Hereditary ovarian cancer
KW - Splicing variant
UR - https://publicatt.unicatt.it/handle/10807/153519
UR - https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85054715383&origin=inward
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85054715383&origin=inward
U2 - 10.1016/j.clinbiochem.2018.10.004
DO - 10.1016/j.clinbiochem.2018.10.004
M3 - Article
SN - 0009-9120
VL - 63
SP - 54
EP - 58
JO - Clinical Biochemistry
JF - Clinical Biochemistry
IS - 63
ER -